BRIGHT AML 1003 study for 111 adults withnewly-diagnosed AML and 14 adults with other conditions for which DAURISMO is not indicated [seeClinical Studies (14)]. Patients were treated with DAURISMO 100 mg daily in combination with low-dose
cytarabine (N=84) or low-dose cytarabine alone (N=41). The median duration of treatment in the DAURISMOwith low-dose cytarabine arm was 83 days (range 3 to 972 days), and the median duration of treatment in thelow-dose cytarabine alone arm was 47 days (range 6 to 239 days). The median exposure to DAURISMO in the
DAURISMO with low-dose cytarabine arm was 76 days (range 3 to 954 days). Thirty-two patients (38%) weretreated with DAURISMO with low-dose cytarabine for at least 6 months and 14 patients (17%) were treated forat least 1 year.
Serious adverse reactions were reported in 79% of patients treated in the DAURISMO with low-dose cytarabinearm. The most common (≥5%) serious adverse reactions in patients receiving DAURISMO with low-dosecytarabine were febrile neutropenia (29%), pneumonia (23%), hemorrhage (12%), anemia (7%), andsepsis (7%).
Dose reductions associated with adverse reactions were reported in 26% of patients treated with DAURISMOwith low-dose cytarabine, and the most common reasons (≥2%) for dose reductions due to adverse reactionswere muscle spasms (5%), fatigue (4%), febrile neutropenia (4%), anemia (2%), thrombocytopenia (2%), and
ECG QT prolonged (2%). Adverse reactions leading to permanent discontinuation were reported in 36% ofpatients treated with DAURISMO with low-dose cytarabine, and the most common (≥2%) reasons forpermanent discontinuation were pneumonia (6%), febrile neutropenia (4%), sepsis (4%), sudden death (2%),myocardial infarction (2%), nausea (2%), and renal insufficiency (2%).
Adverse reactions reported in the first 90 days of therapy on the BRIGHT AML 1003 study are shown inTable 2.
Table 2. Adverse Reactions Occurring in ≥ 10% of Patientsa,b Within the First 90 Days of Therapy inBRIGHT AML 1003
Body System Adverse Reactions DAURISMO With
Low-Dose Cytarabine
N=84
Low-Dose Cytarabine
N=41
All Grades
%
Grade ≥ 3
%
All Grades
%
Grade ≥ 3
%
Blood and lymphatic Anemia 43 41 42 37
system disorder Hemorrhagec 36 6 42 12
Febrile neutropenia 31 31 22 22
Thrombocytopenia 30 30 27 24
General disorders and Fatigued 36 14 32 7
administration site Edemae 30 0 20 2
conditions Mucositisf 21 1 12 0
Pyrexia 18 1 22 2
Chest paing 12 1 2 0
Musculoskeletal and
connective tissue disorders
Musculoskeletal painh
Muscle spasmi
30
15
2
0
17
5
2
0
Body System Adverse Reactions DAURISMO With
Low-Dose Cytarabine
N=84
Low-Dose Cytarabine
N=41
All Grades
%
Grade ≥ 3
%
All Grades
%
Grade ≥ 3
%
Gastrointestinal disorders Nausea 29 1 12 2
Constipation 20 1 12 0
Abdominal painj 19 0 12 0
Diarrheak 18 4 22 0
Vomiting 18 2 10 2
Respiratory thoracic and
mediastinal disorders
Dyspneal
Coughm
23
18
11
0
24
15
7
2
Metabolism and nutrition
disorders
Decrease appetite 21 1 7 2
Nervous system disorders Dysgeusian
Dizziness
Headache
21
18
12
0
1
0
2
7
10
0
0
2
Skin and subcutaneous
tissue disorders
Rasho 20 2 7 2
Infection and infestations Pneumoniap 19 15 24 22
Investigations Hyponatremia 11 6 0 0
Platelet count decreased 15 15 10 10 |
